Introduction

This is a 65-year-old female with history of invasive rectosigmoid adenocarcinoma status post low anterior resection complicated by anastomotic dehiscence and pelvic abscess. She underwent sigmoidoscopy with closure of dehiscence with Endo suture. Patient was asymptomatic for 3 years when she presented with rectovaginal fistula, status post failed attempted sigmoidoscopy with Endo suture.

Description

Under general anesthesia first cystoscopy was perfomed and ureteral catheters were places and indocyanine green was injected for identification of the ureters . Uterine manipulator with cup was placed to assist in identification of the rectovaginal space. Laparoscopic portion of the operation started with mobilization of the omentum from the hepatic flexure for later use. Using the images technology ureters were identified and proceeded with posterior cul-de-sac dissection to identify the fistula tract. After the fistula track was identified, surgical clips and sutures from previous failed repair were removed. The rectovaginal space was fully developed and necrotic and nonviable tissue from the vagina and rectal edges were completely removed . Placement of the uterine manipulator in the vagina and the rectal sizer in the rectum facilitated identification of these two organs better. The vagina was closed transversely with one layer of 0 barb sutures and rectum was close in two layers. Finally, mobilized omentum was brought down and placed and secured between the rectum and vagina.

Conclusion/Implications

Patient had no complication intraop and postop and was discharged home on postop day 2. She was seen 2 and 6 weeks postop with no fistula recurrence and is doing well.

Objectives

Ovarian cancer patient experience data is limited, especially in low- and middle-income countries (LMICs). The World Ovarian Cancer Coalition’s online study in 2018 attracted 1531 responses from 44 mainly high-income countries. Recognising the need for robust data to support national efforts to improve women’s survival and quality of life, the Coalition has partnered with the International Gynaecologic Cancer Society to adapt the Study for LMICs.

Methods

An Oversight Committee featuring equal clinical/patient representation from major geographical areas identified 31 potential countries based on income status. The Committee oversees the Study’s adaptation, advises on access issues, and applies a solutions-based approach to challenges.

Results

24 countries with up to 10 centres each are engaged, with a projected sample size of >2,000 women. Countries and even centres vary widely in data collection and service organisation. For some, this is their first national or international collaboration.

Challenges include:

Ensuring participating centres reflect variety of care

Accommodating variability of language, literacy, and internet connectivity (interview, paper, secure electronic link)

Coverage of core expenses (translation, ethics submission)

Ensuring patients and centres with least resource can participate

Developing an equitable approach to publication opportunities

Balancing countries’ differing needs within the study approach

Conclusions

A unified approach among and even within some LMICs is not feasible. A flexible and pragmatic approach with local teams as well as open channels of communication are essential to challenging inequities on this scale. This approach may add complexity to data analysis, but early benefits are being derived as LMIC patient voices are heard.

Objectives

Given the platinum sensitivity of BRCA 1/2-mutated high-grade serous ovarian cancers (HGSC), there is uncertainty about the relative benefits of primary cytoreductive surgery (PCS) versus neoadjuvant chemotherapy (NACT) in this population. We aimed to compare the long-term survival outcomes for women with germline or somatic BRCA mutations with HGSC undergoing either PCS or NACT.

Methods

We conducted a retrospective cohort study of BRCA-associated HGSCs treated with PCS or NACT at a tertiary cancer center between 1991-2020. All patients had confirmed germline or somatic BRCA mutations. Demographics, disease burden, surgical complexity and ten-year overall survival (OS)/recurrence free survival (RFS) were examined.

Results

Of 361 women with germline/somatic BRCA mutations, 240 (66%) underwent PCS and 121 (34%) underwent NACT followed by interval cytoreduction (IDS). Those undergoing PCS were younger (54 vs. 57; p<0.001), but there were no differences in functional status or underlying comorbidities. Initial disease burden was lower in PCS cohort, but surgical complexity was higher. The rate of complete cytoreduction was similar in both groups (22% vs 31%; p=0.120) as well as the rate of Poly (ADP-ribose) polymerase (PARP) inhibitor use (35% vs 32%; p=0.68). The 10-year OS and RFS were superior in PCS cohort (OS 54% vs 25%; p<0.001 and RFS 30% vs 10%; p<0.001). After controlling for CA-125 level, stage, length of cytoreduction, disease burden and surgical complexity, PCS remained as a significant predictor of improved OS (HR 0.46; p=0.002) and RFS (HR 0.56; p=0.004).

Conclusions

PCS leads to superior survival outcomes compared to NACT in women with BRCA-associated HGSC.

Introduction

To investigate the feasibility of laparoscopic secondary cytoreduction in patients with recurrent ovarian cancer with previous laparoscopic primary debulking surgery

Description

Patients: A 52-year-old Korean woman underwent laparoscopic secondary cytoreduction for recurrent ovarian cancer and previous laparoscopic primary debulking surgery

Interventions: Laparoscopy Measurements/Results: A 52-year-old Korean woman had a laparoscopic primary optimal debulking surgery. The FIGO stage IIIC was confirmed and she received 12 cycles of paclitaxel/carboplatin chemotherapy. Since then, it had been checked as NED state for 6 months. During follow up, lab results showed elevation of CA125, and recurrence was confirmed by PET-CT imaging. We performed LAVH with BSO, CDS mass excision, pelvic and para-lymphadenectomy during primary debulking surgery. In addition, diaphragm and omentectomy were performed. She received adjuvant chemotherapy with paclitaxel/carboplatin for 12 cycles. We performed the laparoscopic secondary cytoreductive surgery on November 28, 2017. Peritoneal cavity and diaphragm were clear and showed no metastatic nodule. Metastatic lymph nodes were confirmed along the left iliac vessels like seen in the previous PET-CT imaging and we resected them. What was seen as recurrence around right para-colic gutter area were metastatic nodule on the cecum surface. We removed the nodules and repaired the bowel serosa. She is receiving chemotherapy with stable disease at this time.

Conclusion/Implications

Our experience indicate that laparoscopy is a feasible and safe approach to optimal cytoreduction for patients with recurrent ovarian cancer in case of laparoscopic primary debulking surgery.

Introduction

To demonstrate of identifying one of the renal artery variant, triple renal artery in left during laparoscopic para-aortic lymphadenectomy.

Description

Patients: A 54-year-old Korean woman with postmenopausal bleeding and thickened endometrium> 3cm presented to our department. The histopathology of biopsied endometrium revealed grade 2 endometrioid adenocarcinoma. The preoperative MRI shows an about 6cm sized large volume of tumor within the endometrial cavity.

Interventions: We perform the laparoscopic staging surgery for endometrial cancer. Firstly we performed peritoneal washing cytology, LAVH, BSO, pelvic lymphadenectomy. We designated four area for para-aortic lymphadenectomy. During the procedure in area 4, it was confirmed that two left renal arteries were derived from the trunk of the aorta below the left renal vein. The left lower segmental artery was derived from the middle part of the inferior mesenteric artery and left renal vein. The middle segmental artery was derived just below left renal vein. The left main renal artery was located on the dorsal side of the left renal vein at its normal position. We carefully resected the para-aortic lymph nodes to prevent variant renal artery damage.

Conclusion/Implications

Laparoscopy is a feasible and safe approach to diagnosis of vascular anomaly during para-aortic lymphadenectomy for gynecologic malignancies. It is very important for the gynecologic oncologist to have knowledge of retroperitoneal vascular anatomy, experience in laparoscopic surgery, and an accurate surgical technique to avoid vascular injury during laparoscopic para-aortic lymphadenectomy.

Introduction

To present laparoscopic restasing surgery for ovarian cancer mimicking a parasitic myoma discovered during LAVH for huge uterine adenomyosis after HIFU.

Description

A 49-year-old Korean woman with severe dysmenorrhea and abnormal uterine bleeding to our department. She had received High intensity focused ultrasound (HIFU) for adenomyosis six years ago. Pelvic MRI showed typical adenomyosis feature with huge uterus with ill-defined myometrial lesion. We planned to perform laparoscopically assisted vaginal hysterectomy on September 13 2021. We discovered small mass mimicking parasite myoma on right paracolic gutter. After hysterectomy, we removed the myoma like mass and the mass was sent frozen section histological analysis revealed a diagnosis of serous carcinoma. We performed abdominal exploration and washing cytology. Additionally, we discovered small tumor nodules on both ovarian surface covered by huge adenomyoma. We finished the initial surgery to do baseline study for ovarian cancer. We performed the laparoscopic restaging surgery for ovarian cancer after baseline study on September 30, 2021. The FIGO stage IIIC was confirmed based on the final histopathological result.

Conclusion/Implications

Laparscopic restaging surgery for ovarian cancer mimicking a parasitic myoma discovered during LAVH for huge uterine adenomyosis after HIFU was safe and successful.

Objectives

Clinical data across several solid tumors, including EC, suggests synergy between immune checkpoint inhibition and anti-angiogenic agents. This study sought to evaluate the efficacy and safety of Atezolizumab (A) and Bevacizumab (Bev) in recurrent EC.

Methods

This multicenter, single arm trial (NCT03526432) enrolled patients with recurrent EC (1-2 priors) to receive A 1,200mg and Bev 15 mg/kg day 1 every 21 days. The primary endpoint was overall response rate (ORR) and duration of response (DOR).

Results

There were 57 response evaluable patients who received both drugs for the first two cycles. Median age was 65 (25-91) years and race included 22.8% Black and 2% American Indian. 61% had endometrioid tumors, 18% UPSC or carcinosarcoma each and 4% clear cell. 87% were mismatch repair proficient (MMRp) and 13% MMRd. 15% had prior pelvic radiation. Adverse events and clinical activity in Table 1. Translational data including blood immune cell population analysis by CyTOF will be presented with the clinical data.

Conclusions

The ORR for A and Bev approximates that seen with Len/Pem with far fewer side effects. An ongoing trial within the Alliance contains this similar arm and if confirmatory would support this combination as a treatment option.

Objectives

Several studies have investigated whether patients with prior breast cancer (BC) are at increased risk for endometrial cancer/uterine serous cancer (USC). We aimed to study this relationship and analyze the effect of prior BC on the incidence and prognosis of USC patients.

Methods

With permission of the Surveillance, Epidemiology and End Results (SEER) program of the United States National Cancer Institute, clinicopathological information of women diagnosed with BC and following USC were analyzed. The recorded data included age at diagnosis, stage of disease, cause of death, interval time between BC and USC diagnosis and overall survival.

Results

The SEER database included 10021 patients with USC during the years 1975-2015. 698 (6.96%) of these patients had been previously diagnosed with breast cancer (BC).

The incidence of USC in patients with BC history was 57 times higher than in women without BC history (p value < 0.001). The incidence of USC did not differ between ER positive and ER negative BC patients (p. value 0.94). The mean survival of USC patients with previous BC history was 8 years (96 months, 95% CI 85.7-106.2), shorter than in USC patients with no BC history presenting a mean survival of 10.6 years (127 months, 95% CI 124.0-130.8) (p. value =0.002).

Conclusions

Our results highlight the relationship between BC and USC, suggesting an increased risk for USC among BC patients. This clinical association should be introduced to BC patients, and physicians should be alert to any EC presenting symptom in BC survivors.

Objectives

Mirvetuximab soravtansine (MIRV) is a first-in-class ADC comprising a folate receptor α (FRα)-binding antibody, cleavable linker, and maytansinoid DM4 payload. Here, we present updated data from the single-arm study SORAYA on the clinical benefit and safety of MIRV in FRα-high platinum-resistant ovarian cancer (PROC).

Methods

Patients (N=106) received MIRV 6 mg/kg, adjusted ideal body weight, intravenously on Day 1 of a 3-week cycle. Patients must have received 1-3 prior therapies, including bevacizumab. FRα-high expression by immunohistochemistry (PS2+ ≥75%) was required. Responses were assessed by investigator using RECIST v1.1. Here we report tumor reduction and disease control rate (percent of patients with complete response, partial response, and stable disease of 12+ weeks).

Results

Characteristics of 106 patients enrolled are in Table 1.

Seventy-five patients (71%) experienced tumor reduction as their best response (Figure 1) and the disease control rate (DCR) was 51.4% (95% CI 41.5, 61.3). The confirmed ORR was 32.4% (95% CI 23.6, 42.2), the median duration of response was 6.9 months (95% CI 5.6, 8.1), and the median progression-free survival was 4.3 months (95% CI 3.7, 5.1).

Most frequent treatment-related adverse events (TRAE; all, grade 3+) related to study drug included blurred vision (41%, 6%), keratopathy (36%, 9%), nausea (29%, 0%), and dry eye (23%, 2%). Seven percent of patients discontinued treatment due to a TRAE.

Conclusions

MIRV demonstrated anti-tumor activity by tumor reduction and DCR in heavily pretreated patients with FRα-high PROC. These data support MIRV as a potential practice-changing, biomarker-driven therapy.

Objectives

Early reports of PD-1 inhibition in ovarian clear cell carcinomas demonstrate promising durable response. We evaluated the combination of pembrolizumab and IDO-1 inhibitor epacadostat in patients with recurrent ovarian clear cell carcinomas.

Methods

This single arm, two-stage, phase 2 trial included those with measurable disease and 1-3 prior regimens. Patients received intravenous pembrolizumab 200 mg every 3 weeks and epacadostat orally 100 mg twice a day. Primary endpoint was overall response rate (ORR), with secondary endpoints of toxicity, progression-free survival (PFS) and overall survival (OS).

Results

Between September 28, 2018 and April 10, 2019, 14 patients accrued at first stage. Rate of accrual was 2.3 patients per month, higher than estimated. Median age was 65 (44-89), 10 (71.4%) had ≥ 2 prior regimens. ORR was 21% (95% CI 5-51%) within 7 months of study entry with 3 partial responses, 4 had stable disease for disease control rate of 50%. Median PFS was 4.8 months (95% CI: 1.9-9.6), OS 18.9 months (95% CI: 1.9-NR). Most common grade ≥ 3 adverse events reported were electrolyte changes and bowel obstruction. In July 2019, the study reached the pre-specified criteria to re-open to second stage, however after holding for amendment, the study closed prematurely in February 2021 due to insufficient drug supply.

Conclusions

Combination of pembrolizumab and epacadostat demonstrated an ORR of 21% in this small cohort of recurrent ovarian clear cell carcinomas. The rapid rate of accrual highlights the enthusiasm and need for therapeutic studies in patients with ovarian clear cell carcinomas.

Objectives

Evaluate the prevalence of alterations in homologous recombination DNA damage repair genes (HR-DDR) among patients with uterine sarcomas.

Methods

The AACR GENIE v12.0 database was accessed and patients with uterine leiomyosarcoma, adenosarcoma and endometrial stromal sarcoma were identified. We examined the incidence of pathogenic alterations of genes involved in HR-DDR: ATM, ARID1A, ATRX, BAP1, BARD1, BLM, BRCA2, BRCA1, BRIP1, CHEK2, CHEK1, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, MRE11, NBN, PALB2, RAD50, RAD51, RAD51B, RAD51C, RAD51D, WRN.

Results

A total of 433 patients contributing to 450 samples were identified; 298 patients with leiomyosarcoma (LMS), 53 patients with adenosarcoma (AS), 30 patients with low-grade endometrial stromal sarcoma (ESS), 19 patients with high-grade, and 34 patients with ESS not specified (34 samples). The overall incidence of pathogenic HR-DDR gene alterations was 30% (135/450). The most prevalent gene alteration was ATRX (20%, 84/419) followed by BRCA2 (5%, 20/416), RAD51B (4%, 10/271), ATM (2.2%, 10/446) and ARID1A (1.9%, 8/419). The highest incidence of HR-DDR gene alterations was observed in leiomyosarcoma (36.5%) followed by adenosarcoma (29.8%), and HG-ESS (26.3%) while HR-DDR gene alterations were less common in ESS NOS (17.7%) and LG-ESS (13.3%). In the present cohort, incidence of TP53 mutations was 49% (213/432), while other common pathogenic gene alterations included the RB1 (29%, 128/449), PTEN (13%, 58/449) and MED12 (11%, 42/375) genes.

Conclusions

Approximately 1 in 3 patients with uterine sarcoma, harbor a pathogenic alteration in HR-DDR genes. These results provide further rationale for the design of molecularly driven clinical trials exploring agents targeting DNA damage repair.

Objectives

Everolimus-based treatment (ET) has proven efficacy in recurrent endometrial cancer (EC). The association of mutations found in biopsy specimens and response to ET is unclear.

Methods

We performed a retrospective review of pts with EC treated with everolimus from 3/2016 to 12/2021. Next generation sequencing data were collected for KRAS, PIK3CA, CTNNB1, TP53, and PTEN mutations. The objective response rate (ORR) and clinical benefit rate (CBR at 6 months) were assessed. Chi-squared or Fisher’s exact tests were used to analyze CBR differences between groups. Kaplan Meier methods were used to estimate survival (PFS and OS), modelled via Cox proportional hazards.

Results

89 patients were included. Average age at diagnosis was 59.9 years. The majority (62.9%) had endometrioid histology and 87.6% received everolimus and AI +/- metformin. ORR was 40.0% (95% CI: 29.2 – 51.6%). CBR was 67.5% (95% CI: 56.1 – 77.6%). Median PFS was 5.98 months (95% CI: 4.57 – 8.28). TP53 wildtype had ORR 52.4% (95%CI: 36.4-68.0%) v 22.7% (95%CI: 7.8-45.4%) in TP53 mutants. TP53wt had CBR 85.7% (95%CI: 71.5-94.6%) v 40.9% (95%CI: 20.7-63.6%) in TP53 mutants. Median PFS in TP53wt was 11.43 months v 2.76 months in TP53 mutants (P<0.001). CTNNB1 mutations were associated with improved response with 87.5% CBR (95%CI: 67.6-97.3%) v 60.0% (95%CI: 43.3-75.1%) in CTNNB1wt. PIK3CA mutations were associated with worse survival (median OS 11 months v 28 months in PIK3CAwt (P<0.045)).

Conclusions

Molecular findings may help predict treatment response to ET. Further exploration of the correlation between mutations and treatment response in a larger prospective population are needed.